Quadrature generators based on ring oscillators and shift registers

Quadrature oscillators are key elements in modern radio frequency (RF) transceivers and very useful nowadays in wireless communications, since they can provide: low quadrature error, low phase-noise, and wide tuning range (useful to cover several bands). RC oscillators can be fully integrated without the need of external components (external high Q-inductors), optimizing area, cost, and power consumption. The conventional structure of ring oscillator offers poor frequency stability and phasenoise, low quality factor (Q), and besides being vulnerable to process, voltage and temperature (PVT) variations, its performance degrades as the frequency of operation increases. This thesis is devoted to quadrature oscillators and presents a detailed comparative study of ring oscillator and shift register (SR) approaches. It is shown that in SRs both phase-noise and phase error are reduced, while ring oscillators have the advantage of occupying less area and less consumption due to the reduced number of components in the circuit. Thus, although ring oscillators are more suitable for biomedical applications, SRs are more appropriate for wireless applications, especially when specification requirements are more stringent and demanding. The first architecture studied consists in a simple CMOS ring oscillator employing an odd number of static single-ended inverters as delay cells. Subsequently, the quadrature 4-stage ring oscillator concept is shown and post-layout simulations are presented. The 3 and 4-phase single-frequency local oscillator (LO) generators employing SRs are presented, the latter with 50% and 25% duty-cycles. The circuits operate at 600 MHz and 900 MHz, and were designed in a 130 nm standard CMOS technology with a voltage supply of 1.2 V.

Experimental determination of bone cortex holding power of orthopedic screw

Cylindrical specimens of bone measuring 15 mm in diameter were obtained from the lateral cortical layer of 10 pairs of femurs and tibias. A central hole 3.2 mm in diameter was drilled in each specimen. The hole was tapped, and a 4.5 mm cortical bone screw was inserted from the outer surface. The montage was submitted to push-out testing up to a complete strip of the bone threads. The cortical thickness and rupture load were measured, and the shear stress was calculated. The results were grouped according to the bone segment from which the specimen was obtained. The results showed that bone cortex screw holding power is dependent on the bone site. Additionally, the diaphyseal cortical bone tissue is both quantitatively and qualitatively more resistant to screw extraction than the metaphyseal tissue.

The use of bone bridges in transtibial amputations

We sought to describe the bone bridge technique in adults, and present a variation for use in children, as well as to present its applicability as an option in elective transtibial amputations. This paper presents a prospective study of 15 transtibial amputations performed between 1992 and 1995 in which the bone bridge technique was employed. The patients' ages ranged from 8 to 48 years, with an average of 22.5 years. This technique consisted of the preparation of a cylinder of periosteum extracted from the tibia and with cortical bone fragments attached to it to promote a tibiofibular synostosis on the distal extremity of the amputation stump. We noted that the cortical bone fragments were dispensable when the technique was employed in children, due to the increased osteogenic capacity of the periosteum. This led to a variation of the original technique, a bone bridge without the use of the cortical bone fragments. RESULTS: The average time spent with this procedure, without any significant variation between adults and children, was 171 minutes. The adaptation to the definitive prosthesis was accomplished between 20 and 576 days, with an average of 180 days. Revision of the procedure was necessary in 3 amputations. CONCLUSIONS: This technique may be employed in transtibial amputations in which the final length of the stump lies next to the musculotendinous transition of the gastrocnemius muscle, as well as in the revision of amputation stumps in children, where the procedure has been shown to be effective in the prevention of lesions due to excessive bone growth.

The use of a modular titanium endoprosthesis in skeletal reconstructions after bone tumor resections: method presentation and analysis of 37 cases

We analyzed 37 patients who underwent segmental wide resection of bone tumors and reconstruction with a modular titanium endoprosthesis at the Orthopaedic Oncology Group, between 1992 and 1998. Twelve patients were male and 25 were female, with a mean age of 30 years (9 - 81). The mean follow-up was 14 months (2 - 48). The diagnoses were: osteosarcoma (14 cases), metastatic carcinoma (10), Ewing's sarcoma (4), giant cell tumor (4), malignant fibrous histiocytoma (3), chondrosarcoma (1), and aneurysmal bone cyst (1). Eleven articulated total knee, 8 partial proximal femur with bipolar acetabulum, 8 partial proximal humerus, 3 total femur, 2 partial proximal tibia, 2 diaphyseal femur, 2 diaphyseal humerus, and 1 total proximal femur with cementless acetabulum endoprosthesis implant procedures were done. The complications related to the procedure included: infection (5 cases), dislocation (3), module loosening (1), and ulnar nerve paresthesia (1). We used the following criteria for the clinical evaluation: presence of pain, range of motion, reconstruction stability, surgical and oncologic complications, and patient acceptance. The results were good in 56.8% of the cases, regular in 32.4% and poor in 10.8%.

Widespread hematogenous metastases and Trousseau's syndrome in gastric adenocarcinoma

A case of widespread hematogenous metastases and Trousseau's syndrome is reported in a 40 year-old white housewife with gastric cancer, presenting subdural hematoma, ecchymoses, epistaxis, stomach and uterine bleeding. After undergoing hematoma drainage, she was unsuccessfully treated with platelets, red blood cells, plasma cryoprecipitate transfusions, and antibiotics. Necropsy disclosed gastric ring-signet adenocarcinoma invading the serous layer, with massive disseminated intravascular coagulation and systemic neoplastic embolism. Multiple old and recent hyaline (rich in fibrin and platelets) microthrombi, and tumor emboli were observed in the bone marrow, meninges, liver, lungs, kidneys, lymph nodes, adrenals, thyroid, heart, pancreas, and ovaries (Krukenberg tumor).

Normal bone density in male pseudohermaphroditism due to 5alpha- reductase 2 deficiency

Bone is an androgen-dependent tissue, but it is not clear whether the androgen action in bone depends on testosterone or on dihydrotestosterone. Patients with 5alpha-reductase 2 deficiency present normal levels of testosterone and low levels of dihydrotestosterone, providing an in vivo human model for the analysis of the effect of testosterone on bone. OBJECTIVE: To analyze bone mineral density in 4 adult patients with male pseudohermaphroditism due to 5alpha-reductase 2 deficiency. RESULTS: Three patients presented normal bone mineral density of the lumbar column (L1-L4) and femur neck, and the other patient presented a slight osteopenia in the lumbar column. CONCLUSION: Patients with dihydrotestosterone deficiency present normal bone mineral density, suggesting that dihydrotestosterone is not the main androgen acting in bone.

The effect of the presence of muscle tissue in a bone healing site

PURPOSE: The recovery of a bone fracture is a process that is not yet fully understood. The literature conflicts on the results obtained by the interposition of foreign tissue inside a damaged bone. The objective of the present study was to ascertain the effect of placing muscle tissue between the stumps of a fractured bone. METHOD: The study was carried out on 10 rabbits divided into 2 groups (n = 5): Group 1-partial fracture of the humerus and interposition of muscle tissue; Group 2-complete fracture of the humerus and interposition of muscle tissue. The fractured limb of all animals was immobilized for 8 weeks. At the end of this time, the rabbits were killed and their operated humeri were carefully removed for roentgenological and histological assessment. RESULTS: All humeri of Group 1 recovered their integrity and normal aspect. However, the healing of the humeri of Group 2 was not perfect. Gross angulation of the bone diaphysis occurred in all animals, and immature trabecular bone, osteochondral tissue, and persistence of muscle tissue substituted normal bone. CONCLUSIONS: Interposed muscle does not affect partial bone fracture healing but causes instability in a complete fracture.

Retrospective evaluation of bone pain palliation after samarium-153-EDTMP therapy

PURPOSE: The aim of this study was to evaluate the degree of metastatic bone pain palliation and medullar toxicity associated with samarium-153-EDTMP treatment. METHODS: Seventy-three patients with metastatic bone pain having previously undergone therapy with samarium-153-EDTMP (1 mCi/kg) were retrospectively evaluated. Routine follow-up included pain evaluation and blood counts for 2 months after treatment. Pain was evaluated using a subjective scale (from 0 to 10) before and for 8 weeks after the treatment. Blood counts were obtained before treatment and once a week for 2 months during follow-up. Dosimetry, based upon the urinary excretion of the isotope, was estimated in 41 individuals, and the resulting radiation absorbed doses were correlated with hematological data. RESULTS: Reduction in pain scores of 75% to 100% was obtained in 36 patients (49%), with a decrease of 50% to 75%, 25% to 50%, and 0% to 25% in, respectively, 20 (27%), 10 (14%), and 7 (10%) patients. There was no significant relationship between the pain response and location of the primary tumor (breast or prostate cancer). Mild to moderate myelosuppression was noted in 75.3% of patients, usually with hematological recovery at 8 weeks. The mean bone marrow dose was 347 ± 65 cGy, and only a weak correlation was found between absorbed dose and myelosuppression (Pearson coefficient = .4). CONCLUSIONS: Samarium-153-EDTMP is a valuable method for metastatic bone pain palliation. A mild to moderate and transitory myelosuppression is the main toxicity observed after samarium therapy, showing a weak correlation with dosimetric measures.

Developmental and paleontological insights into skull bone homology and evolution

The Gallus gallus (chicken) embryo is a central model organism in evolutionary developmental biology. Its anatomy and developmental genetics have been extensively studied and many relevant evolutionary implications have been made so far. However, important questions regarding the developmental origin of the chicken skull bones are still unresolved such that no solid homology can be established across organisms. This precludes evolutionary comparisons between this and other avian model systems in which skull anatomy has evolved significantly over the last millions of years.(...)

Silica nanoparticles as dexamethasone delivery systems able to induce the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells

Bioactive glasses, especially silica-based materials, are reported to pres- ent osteoconductive and osteoinductive properties, fundamental char- acteristics in bone regeneration [1,2]. Additionally, dexamethasone (Dex) is one of the bioactive agents able to induce the osteogenic differ- entiation of mesenchymal stem cells by increasing the alkaline phos- phatase activity, and the expression levels of Osteocalcin and Bone Sialoprotein [3]. Herein, we synthesised silica (SiO2) nanoparticles (that present inherent bioactivity and ability to act as a sustained drug delivery system), and coated their surface using poly-L-lysine (PLL) and hyaluronic acid (HA) using the layer-by-layer processing technique. Further on, we studied the influence of these new SiO2-polyelectrolyte coated nanoparticles as Dex sustained delivery systems. The SiO2 nanoparticles were loaded with Dex (SiO2-Dex) and coated with PLL and HA (SiO2-Dex-PLL-HA). Their Dex release profile was evaluated and a more sustained release was obtained with the SiO2-Dex-PLL-HA. All the particles were cultured with human bone marrow-derived mes- enchymal stem cells (hBMSCs) under osteogenic differentiation culture conditions. hBMSCs adhered, proliferated and differentiated towards the osteogenic lineage in the presence of SiO2 (DLS 174nm), SiO2-Dex (DLS 175nm) and SiO2-Dex-PLL-HA (DLS 679nm). The presence of these materials induced the overexpression of osteogenic transcripts, namely of Osteocalcin, Bone Sialoprotein and Runx2. Scanning Elec- tron Microscopy/Electron Dispersive Spectroscopy analysis demon- strated that hBMSCs synthesised calcium phosphates when cultured with SiO2-Dex and SiO2-Dex-PLL-HA nanoparticles. These results indi- cate the potential use of these SiO2-polyelectrolytes coated nanoparti- cles as dexamethasone delivery systems capable of promoting osteogenic differentiation of hBMSCs.

Bioactive nanocomposite spheres with proved shape memory capability in bone defects

Bioactive glass nanoparticles (BGNPs) promote an apatite surface layer in physiologic conditions that lead to a good interfacial bonding with bone.1 A strategy to induce bioactivity in non-bioactive polymeric biomaterials is to incorporate BGNPs in the polymer matrix. This combination creates a nanocomposite material with increased osteoconductive properties. Chitosan (CHT) is a polymer obtained by deacetylation of chitin and is biodegradable, non-toxic and biocompatible. The combination of CHT and the BGNPs aims at designing biocompatible spheres promoting the formation of a calcium phosphate layer at the nanocomposite surface, thus enhancing the osteoconductivity behaviour of the biomaterial. Shape memory polymers (SMP) are stimuli-responsive materials that offer mechanical and geometrical action triggered by an external stimulus.2 They can be deformed and fixed into a temporary shape which remains stable unless exposed to a proper stimulus that triggers recovery of their original shape. This advanced functionality makes such SMPs suitable to be implanted using minimally invasive surgery procedures. Regarding that, the inclusion of therapeutic molecules becomes attractive.  We propose the synthesis of shape memory bioactive nanocomposite spheres with drug release capability.3   1.  L. L. Hench, Am. Ceram. Soc. Bull., 1993, 72, 93-98. 2.  A. Lendlein and S. Kelch, Angew Chem Int Edit, 2002, 41, 2034-2057. 3.  Ã . J. Leite, S. G. Caridade and J. F. Mano, Journal of Non-Crystalline Solids (in Press)

Bone turnover markers for early detection of fracture healing disturbances: A review of the scientific literature

Imaging techniques are the standard method for assessment of fracture healing processes. However, these methods are perhaps not entirely reliable for early detection of complications, the most frequent of these being delayed union and non-union. A prompt diagnosis of such disorders could prevent prolonged patient distress and disability. Efforts should be directed towards the development of new technologies for improving accuracy in diagnosing complications following bone fractures. The variation in the levels of bone turnover markers (BTMs) have been assessed with regard to there ability to predict impaired fracture healing at an early stage, nevertheless the conclusions of some studies are not consensual. In this article the authors have revised the potential of BTMs as early predictors of prognosis in adult patients presenting traumatic bone fractures but who did not suffer from osteopenia or postmenopausal osteoporosis. The available information from the different studies performed in this field was systematized in order to highlight the most promising BTMs for the assessment of fracture healing outcome.

Development of a dextrin-based hydrogel for bone regeneration

[Excerpt] Bone tissue engineering is a very challenging and promising field, which handles with the limitations of bone regenerative capacity and the failure of current orthopedic implants [1]. This work describes the preparation and characterization of an injectable dextrin-based hydrogel (oDex) able to incorporate nanoparticles, cells, biomolecules or Bonelike~ granules [2]. (...)

Gellan gum-coated gold nanorods: an intracellular nanosystem for bone tissue engineering

Gold nanorods (AuNRs) have emerged as an exceptional nanotool for a myriad of applications ranging from cancer therapy to tissue engineering. However, their surface modification with biocompatible and stabilizing biomaterials is crucial to allow their use in a biological environment. Herein, low-acyl gellan gum (GG) was used to coat AuNRs surface, taking advantage of its stabilizing, biocompatible and gelling features. The layer-by-layer based strategy implied the successive deposition of poly(acrylic acid), poly(allylamine hydrochloride) and GG, which allowed the formation of a GG hydrogel-like shell with 7 nm thickness around individual AuNRs. Stability studies in a wide range of pH and salt concentrations showed that the polysaccharide coating can prevent AuNRs aggregation. Moreover, a reversible pH-responsive feature of the nanoparticles was observed. Cytocompatibility and osteogenic ability of GG-coated AuNRs was also addressed. After 14 days of culturing within SaOS-2, an osteoblast-like cell line, in vitro studies revealed that AuNRs-GG exhibit no cytotoxicity, were internalized by the cells and localized inside lysosomes. AuNRs-GG combined with osteogenic media enhanced the mineralization capacity two-fold, as compared to cells exposed to osteogenic media alone. The proposed system has shown interesting features for osteogenesis, and further insights might be relevant for drug delivery, tissue engineering and regenerative medicine.

Biomimetic supramolecular designs for the controlled release of growth factors in bone regeneration

The extracellular matrix (ECM) of tissues is an assembly of insoluble macromolecules that specifically interact with soluble bioactive molecules and regulate their distribution and availability to cells. Recapitulating this ability has been an important target in controlled growth factor delivery strategies for tissue regeneration and requires the design of multifunctional carriers. This review describes the integration of supramolecular interactions on the design of delivery strategies that encompass self-assembling and engineered affinity components to construct advanced biomimetic carriers for growth factor delivery. Several glycan- and peptide-based self-assemblies reported in the literature are highlighted and commented upon. These examples demonstrate how molecular design and chemistry are successfully employed to create versatile multifunctional molecules which self-assemble/disassemble in a precisely predicted manner, thus controlling compartmentalization, transport and delivery. Finally, we discuss whether recent advances in the design and preparation of supramolecular delivery systems have been sufficient to drive real translation towards a clinical impact.